Salvinorin A ameliorates cerebral vasospasm through activation of endothelial nitric oxide synthase in a rat model of subarachnoid hemorrhage

Salvinorin A ameliorates cerebral vasospasm through activation of endothelial nitric oxide synthase in a rat model of subarachnoid hemorrhage
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Salvinorin A 通过激活蛛网膜下腔出血大鼠模型中的内皮一氧化氮合酶改善脑血管痉挛

DOI:
10.1111/micc.12442
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发表时间:
2018-04
期刊:
影响因子:
2.4
通讯作者:
Liu RY
Liu RY
中科院分区:
医学4区
文献类型:
--
作者:
Sun Juan;Zhang Yan;Lu Jianfei;Zhang Weiguang;Yan Junhao;Yang Lei;Zhou Changman;Chen Chunhua;Liu Renyu;Chen CH;Liu RY

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目的:观察丹参甲素(salvinorin A,SA)对蛛网膜下腔出血(SAH)后脑血管痉挛的治疗作用,并探讨其作用机制。方法:SAH后12小时、24小时、48小时、72小时分别腹腔注射丹参素A,观察大鼠神经行为的变化。用磁共振成像(MRI)观察基底动脉。测量基底动脉内径和厚度。检测大鼠海马区CA1区的形态变化和细胞凋亡。采用酶联免疫吸附试验试剂盒检测血浆内皮素-1(ET-1)和一氧化氮(NO)水平。用免疫印迹法检测内皮型一氧化氮合酶(ENOS)和水通道蛋白-4(AQP-4)的蛋白表达,以探讨其可能的机制。结果:丹参甲素可减轻大鼠神经功能障碍,减少神经元凋亡,减轻海马区CA1区的形态改变。SA可通过增加基底动脉内径、减少基底动脉厚度来减轻CVS,并伴有ET-1浓度降低和NO水平升高。同时,SA可增加基底动脉和海马区eNOS的表达,降低AQP-4蛋白的表达。结论:丹参甲素可通过增加eNOS和NO的表达,降低ET-1和AQP-4蛋白的表达,减轻SAH后脑血管痉挛,减轻脑损伤。
Objective: This study aimed to demonstrate the potential of salvinorin A (SA) for cerebralvasospasm after subarachnoid hemorrhage (SAH) and investigate mechanisms of therapeutic effect using rat SAH model. Methods: Salvinorin A was injected intraperitoneally, and the neurobehavioral changes were observed at 12 hours, 24 hours, 48 hours, and 72 hours after SAH. Basilar artery was observed by magnetic resonance imaging (MRI). The inner diameter and thickness of basilar artery were measured. The morphological changes and the apoptosis in CA1 area of hippocampus were detected. Endothelin-1 (ET-1) and nitric oxide (NO) levels were detected by ELISA kit. The protein expression of endothelial NO synthase (eNOS) and aquaporin- 4 (AQP-4) was determined by Western blot for potential mechanism exploration. Results: Salvinorin A administration could relieve neurological deficits, decrease the neuronal apoptosis, and alleviate the morphological changes in CA1 area of hippocampus. SA alleviated CVS by increasing diameter and decreasing thickness of basilar artery, and such changes were accompanied by the decreased concentration of ET-1 and increased level of NO. Meanwhile, SA increased the expression of eNOS and decreased the expression of AQP-4 protein in the basilar artery and hippocampus. Conclusions: Salvinorin A attenuated CVS and alleviated brain injury after SAH via increasing expression of eNOS and NO content, and decreasing ET-1 concentration.and AQP-4 protein expression.
高选择性非阿片 kappa 阿片受体 (KOR) 激动剂 salvinorin A 可预防大鼠前脑缺血引起的脑损伤
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